Natural product diptoindonesin (Dip) G 1 was isolated from tree barks of Hopea mengarawan in Indonesia together with nine other oligostilbenoids in 2009. (L. D. Juliawaty, Sahidin, E. H. Hakim, S. A. Achmad, Y. M. Syah, J. Latip and I. M. Said, Nat. Prod. Commun., 2009, 4, 947.) Around the same time, the same molecule was also isolated from Hopea chinensis stem barks in China. (H. M. Ge, W. H. Yang, Y. Shen, N. Jiang, Z. K. Guo, Q. Luo, Q. Xu, J. Ma and R. X. Tan, Chem. Eur. J., 2010, 16, 6338.) Dip G has a tetracyclic core with A-D rings bearing a ketone and three phenolic OH groups and an additional E-ring with one more phenolic OH group. Dip G showed anti-proliferation effect in murine leukemia P-388 cells (Juliawaty et al., supra) and immunosuppressant activity in a concanavalin A induced proliferation of mouse splenic lymphocytes (T cells) assay. (Ge et al., supra.) Recently, it was reported that Dip G could regulate the stability of estrogen receptor α (ERα) and estrogen receptor β (ERβ), two members of the steroid nuclear receptor superfamily with opposing effect on cell proliferation. (Z. Zhao, L. Wang, T. James, Y. Jung, I. Kim, R. Tan, F. M. Hoffmann and W. Xu, Chem. Biol., 2015, 22, 1608.) ERα promotes cell proliferation, while ERβ has an anti-proliferative effect in breast cancer cells. (A. M. S. Covaleda, H. Van den Berg, J. Vervoort, P. Van der Saag, A. Strom, J.-A. Gustafsson, I. Rietjens and A. J. Murk, Toxicol. Sci., 2008, 105, 303.) Interestingly, Dip G decreases the stability of the oncogenic ERα and increases the stability of ERβ, a tumor suppressor in breast cancer. Instead of directly interacting with ERs, Dip G was found to target the E3 ubiquitin ligase C-terminus of HSC70-interacting protein (CHIP), also known as STIP1 homology and U-Box containing protein 1 (STUB1). (Zhao et al, supra.)
The only total synthesis of Dip G to date was reported by Kim and Kim in 2010, K. Kim and I. Kim, Org. Lett., 2010, 12, 5314.